Acid Reflux Relief : Combination Therapy

Most patients treated with PPIs in conventional dosages do not exhibit complete suppression of stomach acid secretion. Approximately 70% of individuals who take a PPI twice a day experience nocturnal stomach acid breakthrough (defined as a stomach pH lesser than 4 for more than 1 hour at night). Brief episodes of acid reflux occur frequently during these breakthrough periods in patients with GERD. For some patients taking a PPI twice daily, nocturnal acid breakthrough can be abolished by adding a histamine H2-receptor blocker at bedtime. It is not clear that this approach is desirable, however. Complete elimination of acid reflux usually is not necessary to effect the healing of reflux esophagitis. Indeed, most patients who are treated with a PPI in conventional dosage exhibit complete healing of their symptoms and signs of GERD. No clear clinical benefit yet has been demonstrated for the practice of adding a histamine H2-receptor blocker at bedtime to PPI therapy.

A few older investigations have explored the value of combination drug therapy for the healing of GERD. The great efficacy of the PPIs used as single agents in this condition has discouraged investigators from undertaking new studies on combination therapy. Drug combinations that have been studied have included an H2 blocker plus either sucralfate or a prokinetic agent. Cimetidine (1200 mg/d) combined with sucralfate (5 g/d) was found to be superior to cimetidine alone for relieving daytime heartburn and for improving the endoscopic signs of esophagitis. For patients unresponsive to treatment with cimetidine alone, the addition of metoclopramide resulted in symptomatic improvement significantly more often than the addition of placebo, but side effects of metoclopramide were frequent. A combination of ranitidine (300 mg/d) plus metoclopramide (40 mg/d) was not found to be as effective as omeprazole alone (20 mg/d) in healing the signs and symptoms of esophagitis. Some studies explored combination therapy with the prokinetic agent cisapride, but these studies are of historical interest only because cisapride has been withdrawn from general use due to serious side effects (lethal arryhythmias). For patients with moderately severe reflux esophagitis, the use of combination therapy may eliminate the need for treatment with a PPI. However, the addition of a second medication increases the cost of therapy and the potential for side effects. Furthermore, the long-term benefit of combination therapy has not been demonstrated. For patients who are refractory to single-agent therapy (with an H2 blocker, sucralfate, or a prokinetic), a change to a PPI generally is more likely to effect healing than the addition of a second drug.